目的 比较款冬花、叶与紫菀配伍后紫菀散的毒性，为款冬叶的资源利用提供依据。方法 款冬花、叶分别与紫菀（1：1）配伍，小鼠连续给药14 d（生药量40 g/kg），通过组织病理、血清生化指标以及基于¹H-NMR的代谢组学技术对2个复方的毒性进行比较。结果 生化指标和病理学结果显示给药后肝脏发生明显病变；多元统计结合KEGG代谢通路分析确定了血清和肝脏中15个与肝脏毒性相关的生物标志物；从散点图中给药组与对照组的距离及上述生物标志物的变化幅度来看，款冬花、叶配伍的紫菀散虽对机体的代谢影响不同，但未发现款冬叶配伍紫菀后的毒性强于款冬花配伍紫菀后的毒性。结论 款冬叶配伍的紫菀散在毒性上与款冬花配伍的紫菀散相当，为款冬叶的资源利用奠定了研究基础。

Objective To compare the toxicity of two kinds of Ziwansan, which were prepared by Asteris Radix with Farfarae Flos (FF) and the leaves of Tussilago farfara (FL), respectively, The results will provide scientific basis for the utilization of leaves of T. farfarae. Methods The FF and FL were in combination ratio of 1:1 with Asteris Radix, respectively, and given to mice at a dose of 40 g/kg for 14 d. The drug toxicology was evaluated by serum biochemical indicators and histopathological examination, as well as ¹H-NMR based metabonomic approach. Results The mice liver showed obvious damage as revealed by serum biochemical indicators and histopathological examination. Totally 15 biomarkers related to liver toxicity were determined by multivariate statistics and KEGG metabolic pathway analysis. By analyzing the distance between drug treated groups and blank group in scatter plots and the level changes of hepatoxicity related biomarkers, it was found that Ziwansan prepared by FF and FL showed different toxic effects on mice metabolome. However, there was no evidence that Ziwansan made from FL showed stronger toxicity than that made from FF. Conclusion These results suggest that FL and FF show equivalent toxicity in Ziwansan, which lays the foundation for the utilization of leaves of T. farfara.

国家自然科学基金资助项目（31270008）；山西省高等学校创新人才支持计划